Journal of the Indian Chemical Society 98 (2021) 100210

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Journal of the Indian Chemical Society

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A mini review on synthesis, properties and applications of deep

eutectic solvents
Madhur Babu Singh Mr, M.Sc., Vaishnu S. Kumar Mr, B.Sc., Mansi Chaudhary, M.Sc.,
Prashant Singh, Ph.D. *
Department of Chemistry, Atma Ram Sanatan Dharma College, University of Delhi, New Delhi, India

A R T I C L E I N F O A B S T R A C T

Keywords: Organic solvents have been of great importance for many chemical synthesis, storage and separation processes.
Deep eutectic solvents The industries and research laboratories are heavily dependent on organic solvents in bulk; are highly volatile,
Green solvent lipophilic, toxic and causes a number of issues to the human health and the environmental fitness. Neoteric
Futuristic solvent
solvents have been proposed as a better substitute to these harmful organic solvents, and scientists have come up
Applications
with several neoteric solvents in the last three decades, to name a few: ionic liquids (ILs), switchable solvents, bio-
based solvents and deep eutectic solvents (DESs). These neoteric solvents attract a great deal of interest from the
scientific community due to plenty of possibilities, therefore, they have huge impact and novel studies are re-
ported quite frequently on the same. In this review, we intend to focus to brief on deep eutectic solvents, about
their properties, synthesis, promising applications, and how they gradually emerged from ILs and later stood out
as a different class of neoteric solvent, which overcomes many shortcomings of ILs. DESs are possibly receptive
synthetic compounds and their relationship based on the hydrogen bond donor or acceptor restricts their reac-
tivity and allow to explore in different disciplines of science.

Researchers and the industrialists are using the volatile organic sol- A brief about the ionic liquids and their applications
vents in bulk for various purposes like organic and pharmaceutical
chemistry, extraction and others. Organic solvents or the traditional Ionic liquids, by their very name, are liquids and consists of ions;
solvents, are carbon-based molecules with high volatile nature. Owing to remain liquid below 100
C. Its frequently encountered components are
these properties, they are predominantly lipophilic (soluble in fat), Organic cations (e.g. tetraethyl ammonium cation, dialkylimidazolium
flammable, toxic and thus, cause a spectrum of issues to human health cation, 1ethyl-3-methylimidazolium cation) and organic/inorganic an-
and the health of the environment. These causes major neurological ions (nitrate, chloroaluminate, chlorate, thiocyanate, perchlorate, gly-
disorders in humans and hinder important life processes. Moreover, these colate and others) as in Table 1 [4–8]. The presence of at least one of the
are used in plenty of amount and these reign, undoubtedly, over all the organic component maintains the liquid phase of ILs under 100
C.
domains of synthesis, extraction and catalysis [1]. Neoteric solvents, the Further, ILs have relatively high viscosity and density [3,9].
“new solvents”, come off as a better substitute of traditional or conven- It can be attributed to the organic moiety (which is bulky) of ILs that
tional organic solvents. These are the new class of solvents (only being they have a very broad liquidous range and thus incredibly low volatility
studied for over three decades) which are more sustainable, economical, [2]. Such fabulous characteristics of ILs imparts some unique physi-
biodegradable and have its components of biogenic origin as in Fig. 1 [2]. ochemical properties, viz. thermal stability, radioactive stability,
Ionic liquids (ILs), switchable solvents, deep eutectic solvents (DESs) and non-volatility, non-flammability, adjustable miscibility and polarity
bio-based solvents (Bio-Ss) are some of the prominent classes of neoteric [10–13]. The most handy characteristic of ILs are that the aforemen-
solvents. Use of neoteric solvents also minimizes wastes, and they tioned properties could be “Tuned” as per the requirement by choosing
withholds “The twelve Principles of Green Chemistry” [3]. the appropriate cation(s) and/or anion(s), thus forming Task Specific Ionic
Liquids (TSILs) [11,13–16].

* Corresponding author.
E-mail addresses: [email protected] (M.B. Singh), [email protected] (V.S. Kumar), [email protected] (M. Chaudhary), [email protected].
ac.in (P. Singh).

https://doi.org/10.1016/j.jics.2021.100210
Received 27 June 2021; Received in revised form 8 October 2021; Accepted 13 October 2021
0019-4522/© 2021 Indian Chemical Society. Published by Elsevier B.V. All rights reserved.
M.B. Singh Mr et al. Journal of the Indian Chemical Society 98 (2021) 100210

Fig. 1. Organic solvents vs Neoteric Solvents.

Table 1
Common cations and anions of ILs.
Types of cations Types of anions

[PF6]-, [(CF3SO2)2N]-; [BR1R2R3R4]-, [BF4]-, [CF3SO2]-,[CH3CO2]-, [CF3CO2]-, Br-, Cl-, I-,

[NO3]-,[Al2Cl7]-

ILs have revolutionized certain extraction processes. These have [Br] and [TBP] [Br], the opposite phenomenon was seen. The cation has
simplified analytical method development, removal of environmental an impact on the level of toxicity [27].
contaminants, breaking of azeotropes and even purification of fuels. The toxicity of some ILs was reported to be two to four orders of
Preparation techniques like liquid-liquid extraction (LLE) [17], magnitude higher than that of organic solvents. Variation in the toxicities
solid-phase extraction (SPE), pressurized liquid extraction (PLE), novel of ILs and organic solvents are reliant on the experimental species used;
liquid-phase microextraction (LPME) have used ILs with very high effi- thus, toxicological research with different species will be needed. Any
ciency factor (EF). ILs have eliminated the use of chelating agents in assessment of ILs ecotoxicity and toxicity should also include their
selective extraction of ions. ILs can bring about mass transfer in novel overall bioavailability, which is influenced by its low vapor pressures
miniaturized homogeneous LPME models. These have also been used in compared to traditional solvents [28].
UV-Vis spectrophotometric determination of mercury ions from water The toxic effects of ILs were associated to cell membrane breakdown.
samples. Silica, polymers and nanoparticles can support ILs phases and Long alkyl chains are commonly seen in the cationic portion of ILs and
act as SPE sorbents. Silica supported ILs have been used in extraction of enhance the lipophilic nature of the ILs; that increases its capacity to
organic acids, amines, and aldehydes from atmospheric aerosol samples, connect with both the phospholipid bilayer of the cell membrane as well
and as sequestering agent for carbon dioxide [14,18–22]. as the hydrophobic regions of membrane proteins. Physiological pro-
cesses of membrane get disrupted that results in cellular content leakage
Toxicity of ionic liquids and cell death. In unicellular and multicellular test organisms such as
Bacillus subtilis, Saccharomyces cerevisiae, Escherichia coli, Chlamydo-
Ionic liquids are considered “environment friendly” [23,24] mainly monas reinhardti, Caenorhabditis elegans and Scenedesmus quadricauda,
because of their incredibly low vapor pressure and non-flammability, but a potent relationship between toxicity of ILs and the length of the alkyl
their use has been proven to pollute air and potentially harm aquatic and chain was determined [29]. The connection between lipophilicity and
terrestrial ecosystems. Their toxicity varies for every organism at toxicity is known as narcosis (in animals) or basic toxicity (in aquatic
different trophic levels. Various studies have been found that both organism). This phenomenon is based on the fact that increases the
degradation rate and the toxicity of ILs increase as the organic moiety substance's transit through the membrane; raises its concentration in the
becomes bulky. Thus, it is difficult to reduce IL's toxicity without cell that shows harmful effects. Plant's chloroplasts generally have a
compromising its biodegradability [3]. Since, most ILs are water soluble, phospholipid bilayer that may be damaged by ILs, resulting in photo-
waterbodies are most susceptible to accidental discharge or contamina- synthesis inhibition. A guidance and legislature must be set before the
tion. Toxicological studies of ILs showed that ILs have profound effects at use and production of ILs on industrial scale. It is necessary to search for
enzyme level, and also affects bacteria, algae, other cells, aquatic plants, the structure of ILs having low toxicity as well as create a database of
invertebrates and vertebrates [25]. Toxicity of can be affected by cation chemicals structure of environment friendly ILs focused on their toxicity.
structure as well as incubation duration. The toxicity of cyclic compound
having bromide as the anion in [BMIM] and [BMPy] [26] increases with
increasing incubation period. In the case of quaternary salts like [TBA]

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M.B. Singh Mr et al. Journal of the Indian Chemical Society 98 (2021) 100210

Need of an alternative to ionic liquids (ILs) preparation such as purification and waste disposal is not required and
thus large quantities of DESs with little to no waste can be formed [3,30].
The aforementioned toxicity and non-biodegradability of ILs jeopar- The raw components (quaternary ammonium salts and metal salts) of
dizes their use as a neoteric solvent with green affiliation [30]. Moreover, most of DESs are readily available, thus they reduce their production cost
adding the cost of their complex synthesis and its harmful effects make it and their chemical inertness lets us store it efficiently without much
a rather expensive substitute to traditional solvents. Another class of hassle. Their bio-compatibility and bio-renewability is also of great in-
neoteric solvent, DESs, was reported by Abbot et al. in late 2001. They terest to scientific community [30]. Many naturally derived DESs from
observed abnormally deep melting point depression at the eutectic point metabolites, natural deep eutectic solvents (NADESs) have also been
of choline chloride and urea (1:2 equivalent mixture) [31]. DESs are sensational for very obvious reasons [34].
quite commonly regarded as a subclass of ILs as they share many of their
physicochemical properties, namely, low melting points, density, vis- Deep eutectic solvents (DESs)
cosity, incredibly low vapor pressure, non-flammability, chemical and
thermal stability and their properties could be tailored [3,32], but DESs A eutectic mixture is “an approximately reversible isothermal non-
differs in their properties from ILs. DESs compensate many shortcomings reacting mixture between different components during the cooling of a
of ILs, moreover, DESs could also be non-ionic: marks their distinction liquid system, resulting in a depression of the freezing point of the system
from ILs. The potential toxicities, difficulties in synthesis and in comparison to melting points of the pure components” as in Fig. 2. The
non-biodegradability of ILs could be averted by replacing them with eutectic mixture can be binary or of greater number of components.
DESs. In particular to DESs, this depression in melting point of the mixture is
Eutectic mixture can be explained as “an almost reversible or abnormally high-which renders a very broad liquidous range to DESs.
amendable mixture; is isothermal non-reacting between different con- The melting point of this eutectic mixture, or eutectic temperature is
stituents in the course of the liquid system cooling; results in the freezing analogous to a triple point with zero degree of freedom [33]. Abbott et al.
point depression of system as compared to pure compounds Tm” while first reported 1:2 mol fraction mixture of choline chloride with crystalline
the basic definition of DESs – “it is most probably described as complexes urea, with eutectic temperature of 12
C. Herein, abbot et al. explained
of hydrogen bond”. However, between the two constituents of a mixture this “deep” nature of DESs on the basis of hydrogen bond through which
the availability of hydrogen bond is not enough to explain a DES due to species of DESs are aggregated. They defined this mixture to consist of
hydrogen bonding compounds ideal mixture, like DESs of alcohols and hydrogen bond donors (HBDs) and hydrogen bond acceptors (HBAs) as in
fatty acids. The main point of focus in the system of eutectic is the Fig. 3. The Hydrogen bond interaction between these two types of species
depression of melting point. Eutectic point of mixture is an invariant in DESs imparts abnormally low melting point of eutectic mixture thus
which is isobaric and represents the configuration (Teut is lowest melting formed [31].
temperature which is achieved at χeut). At this configuration, the melting DESs are also defined as a system formed from a eutectic mixture of
point is relevant to triple point and it shows the site where solid-liquid Lewis or Brønsted acids and bases with various ionic species - whereas ILs
three (comprise of two different phases of solid and liquid melt of two are consisted of a discrete anion and a cation [35]. It is a ritual to quote
constituent) coincide at equilibrium. the classification of DESs laid down by Abbott et al. They defined DESs
Eutectic mixtures (ESs) can be made by the combination of two or with a general formula R1R2R3R4NþX-. zY- Varying the Y component gave
more components; are cheap and safe and with the presence of hydrogen rise to four different types of Deep Eutectic Solvents as in Fig. 4 [31].
bond between each component, having low melting point. Melting point Since, there is scope for hydrogen bonding between species of DESs and
of ESs is lower than each of the original component. Normally, DESs is water molecules, a majority of them are hydrophilic. This renders them
marked by a freezing point's depression which can be very huge and at futile in extraction process from aqueous media.
temperature 150
C or lower. And many of the deep eutectic mixtures are DESs could be made hydrophobic by using quaternary ammonium
liquid in between the temperature which is 70
C and the room tem- salts with bulky alkyl groups: thereby known as hydrophobic eutectic
perature. DESs share numerous properties, features and characteristics solvents (HESs) [36]. These can be efficiently used in the place of organic
with ILs due to which DESs are now accepted as a category of ILs. Ions in solvents and toxic ILs for extraction from aqueous media. As a result of
ILs are non-symmetric, large, and have low melting points and low lattice the presence of bulky alkyl groups in HESs, their viscosity drops and thus
energy are contained in DESs. These ions are generally acquired with mass transfer between phases is facilitated, moreover, as they are
HBD or metal salt by quaternary ammonium's complexation. For starch's hydrophobic-chances of water contamination is eliminated [37].
chemical change, DESs can be utilized as solvent. DESs likewise display
non-flammability and low vapor pressure [33]. Preparation of DESs
DESs are liquids; are normally clear and viscous with different tones
of color which ranges from white to amber, or below Teut, are cloudy and Since the synthesis of DESs does not require multiple steps or sepa-
opaque solids. Although, solid appearance of DES is to create confusion. ration, no organic solvents are needed. The majority of the DESs com-
Several types of thermal transition aspects are exhibited by DESs in ponents are inexpensive, natural and must be purchased separately in
comparison to numerous standard materials. Depending mainly on the order to prepare the solvent [3]. There will almost certainly be several
nature of their cooling rates and design, many compounds of DESs un- more DESs variations in the coming years, with some of them being
dergo the process of both glass transitions and crystallization. Among immediately available for purchase. Vacuum evaporation, grinding, and
DESs, glass transitions are chief and usual feature, and even under freeze-drying are other methods of DESs preparation. In the evaporating
comparatively modest rate of cooling; DESs can be widespread; for process, the components are discovered in water and the majority of the
instance, go through a glass transition under 5
C/min cooling. The water is evaporated at 323 K in a vacuum. After that, the resulting
dispersal of vitrification which exist among most of the deep eutectic combination is stored in a desiccator containing silica gel until it achieve
solvents indicates at the relationship between molecular dynamics, the a stable weight. The two solid components are combined in a mortar and
properties of observed materials, and the interconnection which may be ground till a clear, homogeneous liquid is produced, usually under ni-
create DES's “deepness” when compared to the other regularly used trogen and/or in a glovebox. Both the HBDs and the HBAs are dissolved
eutectic mixtures. DESs are prepared by intermolecular interactions in approximately 5% water during the freeze-drying process. These two
which is self-associated, most probably done by mixing entropy, in- solutions are combined, frozen, and freeze-dried to form a clear ho-
teractions of van der Waals, bonding of ionic and bonding of hydrogen. mogenous liquid. The most common method of preparation involves
Synthesis of DESs are 100% atom economic as the components are heating and stirring the DESs constituents together in a characteristic
simply mixed to form the eutectic mixture: all the subsidiary steps in the molar ratio in an inert atmosphere until a homogeneous liquid is formed.

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M.B. Singh Mr et al. Journal of the Indian Chemical Society 98 (2021) 100210

Fig. 2. Phase Diagram of a two component system.

Fig. 3. Some common Hydrogen Bond Acceptor and Hydrogen Bond Donors (HBD).

There is no need for an additional solvent, and no traditional reaction with acids and bases have also been found, such as
occurs. As a result, there are no purification procedures is necessary, fructose-sucrose-glucose and malic acid-citric acid,
enhancing their potential as cost-effective replacements to traditional glucose-sorbitol-malic acid, and choline chloride-proline-malic acid.
organic solvents and ILs [33]. NADESs can be prepared similarly, while These components are readily available in plants and thus could lead to a
their components are derived from natural sources. bio-synthesis of NADESs. NMR spectroscopic data of such mixtures
confirmed the extensive hydrogen bonding between the
Natural deep eutectic solvents components-which is a character of an NADESs. Moreover, NMR data of
flower's nectar and honey showed hydrogen bonding between their
Even though ILs and DESs have been proven to be better substitutes composing sugars, thus confirming the existence of NADESs. NADESs
for hazardous traditional organic solvents, their non-biodegradability components have been found in desert plants of the Selaginela genus, such
and toxicity have hindered their development into practical industrial as Mexican moss, as well as microorganisms, lichen, and a variety of
usage [38]. Natural Deep Eutectic Solvents (NADESs) have thus become a other organisms that can survive longer periods without water, such as
hot topic in this domain of study due to their chemical diversity, phar- barley seeds with a high amount of sucrose and choline in the episperm
maceutically acceptable toxicity and biodegradability [39]. Choi et al. during dormancy. NADESs can dissolves macromolecules such as DNA,
hypothesized that NADESs considering that majority of the components proteins, and polysaccharides. This implies that NADESs facilitates the
which are capable of forming DESs were readily available in plants [40, bio-synthesis of water insoluble natural products, and it dissolves both
41], and the NADESs could be an alternate media for bio-synthesis and the substrates and enzymes-which is not possible on taking water [34].
storage of water-insoluble metabolites and macromolecules in living cells
and organisms, thereby, sustaining plant life even in harsh conditions like Properties of DESs
drought and extreme cold [34]. Choline chloride was found to be forming
a plenty of NADES with primary metabolites. Sugar based NADESs [42] The physicochemical properties of DESs trigger a great interest in the

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M.B. Singh Mr et al. Journal of the Indian Chemical Society 98 (2021) 100210

Fig. 4. Classification of DESs.

research community as they associate better with the “Green Chemistry”, components) [44]. However, several other studies demonstrate against
moreover, there is a constant approach to overcome the related short- the aforementioned conclusion. Thus, a greater accuracy in such studies
comings of DESs to procure more practical applications as in Fig. 5 [43]. are still required before we rule out either[3].
Viscosity:
Most of the physicochemical properties of DESs resonate with that of ILs and Liquids's resistance is depicted by the viscosity in reply to deformity at
thus could be substituted for ILs in almost all the applications such as liquid- provided rate. In exercise or in applications, this shows that liquid
liquid extraction (LLE) and separation of phenolic compounds from liquid streams very effectively when the viscosity is low, but if the viscosities
food matrices[3] are higher than flow rate of fluid is slower. Till now, the use of DESs is
Toxicity: A study of choline chloride based DESs, carried out by made difficult in the applications which are used commercially as well as
Juneidi et al. demonstrated that DESs caused less growth inhibition of costly as compared to other choices due to the viscosities of DESs which
various fungi strains (Lentinus tigrinus, Phanerochaete chrysoporium, inclined towards high qualities. Ethaline's viscosity, at 20
C is 52 cP, at
Aspergillus niger and Candida cylindericea) and exhibited greater LC50 similar temperature compare it with water which is 1 cP [32–37,40,41,
(Lethal concentration to kill 50% of the concerned population) compared 45].
to their individual components as well as their aqueous mixture prior to In this process Arrhenius equation is used normally to express the of
the formation of DESs. This also highlights that DESs are rather new DESs viscous behavior:
components, in contrast to being simply a mixture of compounds, with
different properties and toxicities (that is, less toxic than individual ηarrhenius¼ AeE/ RT

Fig. 5. Common properties of DESs.

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M.B. Singh Mr et al. Journal of the Indian Chemical Society 98 (2021) 100210

In this equation, E is expressed in terms of kJ mol-1; A is used to in particular has shown variation in viscosities of DESs as in Table 2.
denote the energy of activation for flow of viscous liquid and R is used as Ionic conductivity: The conductivity of both DESs and ILs are found
molar gas constant. to vary inversely with their viscosity. It has been demonstrated that this
The equation mentioned above only apply those liquid which have phenomenon has its explanation in hole theory. At very high viscosity,
higher temperature or when the measured viscosity with the temperature the no. of holes are feeble, thus, very few free species of DESs and ILs are
of narrow range. The VFT (vogel-fulcher-tammann) for the temperature mobile. Therefore, the conductivity decreases [46]. Moreover, similar to
of wide range this equation is utilized for the viscosity of the liquid. The the viscosities of DESs and ILs, conductivities also vary in compliance to
structure of VFT is normally utilized to define the viscosity of glass liquid Arrhenius-like Theory. The variations are as depicted in Table 3.
which is dependent upon temperature shows the intermolecular inter-
action for example hydrogen bonding and van der Waals and also reflects Density. The density of chloride salts of benzlyammonium as HBA as well
to catch the DESs and viscous behavior of ILs. as the density of ethylene glycol, glycerol, diethylene or triethylene
DESs have very high viscosities (10–1000 Pa); hinders their use as an glycol is measured by the researcher “Basaiahgari et al.”. The outcome of
effective solvent system. Various models have been adopted to explain this shows that the density of DESs is based on glycerol are higher as
this property of DESs. One explanation suggests that extensive hydrogen compared to the density of DESs which are based on ethylene glycol.
bonding between components of DESs render them so viscous as mobility Along with tri-ethylene as well as di-ethylene glycol, the expansion in
of all species is considerably reduced [30]. Preparation of DESs with low ethylene glycol's density was substituted, and the outcome of develop-
viscosity is difficult, as the decrease in hydrogen bonding in order to ment of more bonds of hydrogen (H-bond) is signifies by glycerol because
reduce viscosity leads will compromise with its liquidous range [3]. of expanding the quantity of functional group –OH on HBD, which
An alternate explanation for such high viscosities can be found by apparently diminishes the accessible free volume. Density of Eutectic
considering hole theory-which considers the free volume present in an mixture density can be tunes by the changing the molar proportion as
ionic system. An Arrhenius type variation is observed when viscosities of well as arrangement of HBA to the HBD. Distinct molar ratio of DESs
DESs are studied over a range of temperatures. It is assumed that several based upon ChCl to citric acid were reported in the literature and it was
holes exist in the liquid phase, which move opposite to the solvent's accounted that density is decreases on increasing the ChCl's amount with
species. The solvent species move with the help of adjacent hole. DESs citric acid. Then, on other side, density is increased by the increased
are assumed to be viscous as these holes are way smaller than its com- amount of citric acid [47].
ponents, and thus their mobility is reduced. DESs have generally exhibited higher density than water. The den-
The size (radius) of the hole is temperature and surface tension sities of various DESs vary with changes in the molecular arrangement
dependent, and vary as per the equation: within the DES and its packing. Moreover, densities of DESs were also
observed to be higher than that of their hydrogen bond donors. This has
4(r2) ¼ (3.5 kT)/ γ
been explained by using hole theory, according to which the hole radius
Where k is Boltzmann constant, T is the absolute temperature and γ is the decreases upon formation of DESs from their constituents, rendering
surface tension of the DESs in consideration. This model gives us an them more viscous and denser than their parent compounds. Exact
another window to reduce the viscosity by reducing the surface tension experimental measurements of DESs densities as a function of tempera-
of the DESs (using a surfactant) which increases the hole size and that, in ture can be difficult to come by. As a result, a focus on developing new
turn, increases the ionic mobility [35]. In simple words, DESs with small approaches capable of presenting these data with the greatest degree of
cations and/or mediocre hydrogen bond donors tend to be less viscous precision was imposed [30,48].
[30]. Apart from temperature and surface tension, the nature of DESs Freezing point: The freezing point of a eutectic mixture is of great
components and water content also effect the viscosity of DESs. The significance as it indicates the strength of interaction between the com-
variation in quaternary ammonium salt/organic salt: HBD molar ratio ponents of DESs at eutectic composition as in Fig. 6. The difference be-
tween the theoretical freezing point and the experimental value
obtained, ΔTf, is taken in account for the same, which has been found to
Table 2
vary directly proportional with the strength of the interaction [46]. DESs
Viscosities of DESs at various temperatures.
with freezing point lower than 50
C are of great interest as they could be
Organic Salts HBD Salt: HBD molar ratio Viscosities (cP) used as an alternate solvent in many applications. Most of the DESs which
ChCl Malonic Acid 1:2 1124 (23
C) are room temperature liquids, have carboxylic acids or polyols derived
ChCl CF3CONH2 1:2 77 (40
C) from sugars as hydrogen bond donors. The freezing point of DESs is also
ChCl Sorbitol 1:1 12730 (30
C)
affected by the choice of organic salt that is used [30].
ChCl Imidazole 3:7 15 (70
C)
ChCl Xylitol 1:1 5230 (30
C)
pH: The one another property of DES which is considered to be
ChCl ZnCl2 1:2 85000 (25
C) important is pH or the size of proportion of solution's acidity. As already
EtNH3Cl CF3CONH2 1:1.5 256 (40
C) mentioned before, DESs can be described easily as framework which are
ChCl Urea 1:2 750 (25
C) formed from the combination of acid and base (Lewis or Bronsted); it
ChCl EG 1:2 36 (20
C)
gives the conspicuous thought of pH of DESs. Variation occurs in the pH
ChCl Glucose 1:1 34400 (50
C)
ChCl Urea 1:2 169 (40
C) of DESs depending upon the combination of molar ratio of mixture as
Bu4NBr Imidazole 3:7 810 (20
C)
ChCl EG 1:2 37 (25
C)
ChCl Glycerol 1:2 376 (20
C)
Table 3
ChCl 1,4-Butanediol 1:3 140 (20
C) Physical Properties of some common DESs.
ChCl EG 1:3 19 (20
C) DES (mole ratio) Density Viscosity Conductivity Surface tension/
ChCl 1,4-Butanediol 1:4 88 (20
C) /g cm-1 /cP /mS cm-1 mN m-1
ChCl Glycerol 1:2 376 (20
C)
ChCl EG 1:4 19 (20
C) ChCl:Urea(1:2) 1.24 632 0.75 52
EtNH3Cl Acetamide 1:1.54 64 (40
C) ChCl:ethylene glycol 1.12 36 7.61 49
ChCl Glycerol 1:3 450 (20
C) (1:2)
ChCl Glycerol 1:4 503 (20
C) ChCl:glycerol (1:2) 1.18 376 1.05 55.8
AcChCl Urea 1:2 2214 (40
C) ChCl:malonic acid – 721 0.55 65.7
EtNH3Cl Urea 1:1.5 128 (40
C) (1:1)
Bu4NBr Imidazole 3:7 810 (40
C)
A less viscous and better conducting DESs are to be explored in order to replace
ZnCl2 Urea 1:3.5 11340 (25
C)
the aqueous electrolytes [46].

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M.B. Singh Mr et al. Journal of the Indian Chemical Society 98 (2021) 100210

Fig. 6. Variation of freezing point and the depression in freezing point of metal salts' and amides' 2:1 mixture with choline chloride. Each data point represents
different mixtures.

well as relying upon the cationic and anionic mixture's relative acidity. well as direct estimation of vapor pressure of DESs has been executed.
The acidity of the combinations is defined the characteristics of frame- DESs are archetypical type like glyceline, reline, ethaline, and it is stated
work's different attributes as well as it is also crucial in the mechanical by these writers that in all three mention above most volatile is ethaline,
applications and have a scope in future. In the experimental work of and this can be given on premise of that 2 significant degrees of ethylene
“Hayyan et al.” it is seen that, he included the study of the pH of DESs of glycol which have more V.P. as compared to glycol.
the different molar combinations of the ChCl along with D-glucose. And REFRACTIVE INDEX: When light goes through a medium, the light's
through this study it is observe that the pH of the mixture is remain speed is changes with respect to the light's speed in the vacuum it is
nearby 7 in the temperature range from 25
C to 45
C, and shows that measures by the refractive index (also signifies as dimensionless property
mixture is neutral, by all this it is conclude that this combination is not of material). Consider the snell's law:
depend upon temperature, and can used for industrial purpose [49]. On
the other hand, the dependence of pH on increasing temperature is also n ¼ c/ν
observed when the temperature is rises from 25
C to 84
C. The same In several examinations, the refractive index was likewise supposed to
pattern is also shown by the other scientist whose name is Skulcove et al. rely upon the HBD types in DESs. In the studies of Hong Zhen et al. [53]
[36–42,45,46,50][]. []. []. []. investigated that with the rise in the examined that few DESs with the similar HBA dependent on differing
temperature, a linear lowering of pH is observed. A huge distinction in HBDs (HBA used TBAC, tetrabutylammoniumchloride). In all the tried
values of pH is observed which are relying upon the used HBD. HBDs the refractive index of DESs which is composed of 2:1 the study of
IONIC CONDUCTIVITY: From an essential perspective, the effective DESs properties which are electrochemical, refractive index could be
flow of ions as well as the effective flow of current permitted by the used.
material with the ionic conduction's mechanism is evaluated by Ionic HYDROGEN BONDING: As seen by many publications in the recent
conductivity. And for the purpose of research, the conductivity of DEs has years, it has been noted that on fundamental of DESs, hydrogen bonding
been the main interest, include the applications of power system for behaves as a main intermolecular force for the depression in the M.P. that
instance, their utilization potentially in electrolytes [51] for the batteries happens in the course of DESs formation along with contribution of ions
of redox-flow. Compare to molten-salts with higher temperature, DES's as well as steric effects of cation/anion set. Although, hydrogen bonding
ionic conductivity is lower (BiCl3 - 350 mS cm-1 and ethaline – 6.17 mS phrase represent a non-understand numerous behaviors by several re-
cm-1 at temperature 200
C and 20
C, respectively). searchers to adequate explanator of real behavior; is literally available in
SURFACE TENSION: To expand the material's surface area, there is a bonds which construct in DESs framework. As reported by IUPAC on the
requirement of energy's proportion; is surface tension. Surface tension is topic, charge is transferred in between the species of HBA as well as HBD
identified with material's propensity to have littlest conceivable surface and this bond of hydrogen is electrostatic in behavior naturally. Due to
area. In DESs, surface tension could be estimated by conductivity of ions, the charge transfer occurs in between HBA and HBD “partially covalent”
consistency as well as thickness like as methods for known changes in the bond formation is obtained, and it is detected by NMR or FTIR (Fourier
DESs molecular climate because of changes in temperature and also in transform infrared spectroscopy or Nuclear magnetic resonance spec-
structure. The surface tension of DESs based on three ChCl with phenol, troscopy respectively) [54]. In the examination of framework of
ethylene glycol HBDs as well as levulinic acid is investigated. The hydrogen bond, the use of M.P. estimation, viscosity as well as density is
composition of DESs for eutectic of ChCl:D-fructose was 2:1, and it is proceeds to explain by Pimentel, which greatly correlates with latest field
identified by the help of measurements of freezing point. Some other of focus in the studies of DESs. For instance, the general guidelines, which
theories also reported for the fortunate growth of DESs and assuming its is designate to connect with Hydrogen bonding with changes formed in
surface tension, which can be used for comparing data between surface its density. Commonly, when the density is increased, the formation of
tension which is determined experimentally with empirical models [52]. latest H-bond occurs due to which framework's molar free volume
VAPOR PRESSURE: In the equilibrium of thermodynamics, the decreases.
pressure on vapor phase is imposed by the phase of vapor along with its
condensed phase. And in this context, it shows the closeness with the ILs,
Applications of DESs
and in past, it is not uncommon for the writer to identify vapor pressure
which is negligible as a characteristic which may be usual to DESs. If
Deep eutectic solvents are being explored in different applications
considered factually, few theories were available; where the indirect as
and some of them are mentioned in Fig. 7.

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M.B. Singh Mr et al. Journal of the Indian Chemical Society 98 (2021) 100210

Fig. 7. Various applications of Deep Eutectic Solvents.

Purification of Biodiesel: Owing to their very high polarity, DESs of DESs and biodiesel. 1H-NMR data of biodiesel was investifated after
are easy and efficient substitute for aqueous an traditional organic sol- removal of DES showed considerable decrease in the moles of glycerol in
vents in separation of polar substances. Glycerol, a fairly polar compound it. This approach could thus be efficiently used to purify biodiesel. The
is formed as a by-product in the synthesis of biodiesel, which is required 1:2 M mixture of acetylcholine chloride-glycerol was able to remove 99%
to be removed from the biodiesel before it could be approved by set of glycerol from biodiesel. The following Fig. 8 depicts the increase in
standards for their use in vehicles. Generally, glycerol is removed by moles of glycerol in DES (ChCl-glycerol) after their retrieval from bio-
liquid-liquid phase decantation but it requires vigorous steps beyond diesel over time.
that, to be fit for use in vehicle. It was speculated that this residual Moreover, DESs with chloride anion were more efficient in glycerol as
glycerol could be extracted by adding a quaternary ammonium salts to compared to the ones with bromide anion, which could be attributed to
the mixture so as to spontaneously form deep eutectic mixture with it the greater electronegativity of the former. Choline chloride/glyceride
[55], thereby, removing glycerol from the biodiesel. But this approach DES (1:1 mol ratio) and phosphonium bromide based DESs were also
didn't retrieve expected results. efficient in extraction glycerol from palm oil-based biodiesel. Mono-
DESs do not mixed with biodiesel although they are miscible with glycerides and diglycerides, apart from glycerol could also be extracted
water. The detachment or separation oil of soya bean from glycerol is using DESs [30,48].
considered to be troublesome for this situation because soya bean was Dissolution of Gases: DESs are very efficient in storing solutes in
picked as crude material. In the beginning, the formation of DES is un- them in scientific jargon, DESs have very high distribution coefficient of
expectedly or spontaneous along with glycerol residues present in bio- solutes. Use of DESs in SO2 sequestration of fuels and CO2 capture has
diesel; salts of quaternary ammonium were added straightforwardly to gained popular attention. Oxidized sulfur compounds could be easily
the biodiesel which is crude or raw biodiesel. DESs showed high extracted by hydrophilic DESs [56,57]. CO2 capture in DESs gives way
extraction proficiency might be ascribed to high electro-negativity of too many fabulous applications of DESs: namely, separation and purifi-
chloride ion. Salts of quaternary ammonium were isolated from the DESs; cation of gas, catalysis, and chemical fixation of CO2.
are saturated by the process of re-crystallization from the compound 1- It was of a great interest to Han et al. to study the solubility of CO2 in
butanol, however, this interaction is not extremely effective. DESs (Reline) and factors which affected its solubility. Their work
Abbott et al. proceeded to mix DESs in biodiesel in speciifc mole ratio significantly suggested that solubility of CO2, considering its mole

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M.B. Singh Mr et al. Journal of the Indian Chemical Society 98 (2021) 100210

Fig. 8. Mole fraction of glycerol residue in biodiesel in AcChCl-glycerol based DESs, varying with time.

fraction in DESs, depends on three major factors: alloying, recovery, and smelting all these processes are incorporated by
DES strategies to give functional stock materials from raw as well as
i. Solubility of CO2 in reline was directly proportional to the pres- recycled sources, permitting an instant precursor for working of metals
sure of the gaseous CO2. and another different application that make use of metals in the forma-
ii. Solubility of the CO2 vary substantially at lower pressure range of tion of variation of useful tools. Most of the latest technologies depend
CO2. upon renewable, cheap and good availability of these materials which are
iii. Solubility of CO2 in reline varied inversely with respect to tem- raw materials, and DESs provide the chance of latest and upgraded
perature, irrespective of CO2 pressure. metallurgical practices is attractive. This nerve afterwards led to the
work on the processes of electrochemical of metal deposition, processing
DESs mixture showed higher solubility in 1:1 ratio than 1:1.5 and and dissolution. In deep eutectic solvents, the solubility and conductivity
1:2.5 mixture. Water content of some DESs (hygroscopic) significantly of metals salt's has been exploited.
reduced their gas retention property, thus water acts as an antisolvent in Solvation of Metal Oxides in DESs: The hydrogen bonding property
the eutectic mixture which drives CO2 out of DESs. Owing to the of DESs render them a very efficient dissolution properties. A variety of
incredibly low vapor pressure of DESs, the vapor at the surface of the compounds, even which are seldom soluble in water, are readily soluble
DESs and CO2 mixture can be considered to be 100% CO2 at lower in DESs. The same also comes in handy for dissolving metal oxides,
temperature range, thus giving us a way to calculate the Henry's Constant thereby enabling us to separate and recycle metals as in Table 4. Abbott
of CO2 in various DESs [58]. Metal-organic framework has been also and team studied the dissolution of ZnO, Fe3O4, CuO in DES of choline
developed which captures a wide variety of gases [59]. Gas capturing chloride with malonic, phenylpropionic and propionic acids [31].
property of DESs can be utilized in containing global warming [35]. DESs On the other hand, oxides of aluminum and silicon are rendered
have also been used in the synthesis of carbon nanosheets with tunable insoluble in DESs, thus giving us a strategy to selectively extract metals
thickness, which could separate carbon dioxide from nitrogen gas [60]. from their mixtures.
Most of the DESs could be used widely in the process of separation. The electrospray mass spectroscopy of metal oxides mixture in reline
Separation is the process which broadly related to the industries for the suggested the ability of DESs to dissolve metal oxides due to metal ox-
processing of chemicals and this process includes physical separation of ides’ complexation with urea and chloride anions. UV-Visible spec-
more than or two or two components from a mixture. Most of the current trometry studies of CuO also suggested the same. DFT calculations of CuO
matters in the industry of chemical processing have to done along with in reline suggested that urea and chloride formed hydrogen bonds, thus
undesirable compound's production as derivative; as considerable
amount of research in applications of DES area has been administered Table 4
towards separations. Solubility of Various metal oxides in DESs at 500C.
Metallurgy: In DESs, metallurgy is the first topic which create in- DESs Solubility (mol/L)
terest as a solvent and during this time it was observed that in DESs
CuO ZnO Fe3O4
conductivity which is electrical and high solubilities exhibited by metals
and salts of metals, and it makes them favorable compound for refining of ChCl/malonic acid 0.246 0.554 0.071
ore, in solution-extraction of metals, electro-deposition Purification, ChCl/phenylpropionic acid 0.473 >0.491 0.014
ChCl/oxalic acid 0.071 0.491 0.341

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M.B. Singh Mr et al. Journal of the Indian Chemical Society 98 (2021) 100210

attaining an open structure, which facilitated proton transfer on tem- compounds play a pivotal role on organic synthesis and complete syn-
perature rise or complexation with metal [61]. thesis of bio-active compounds. DESs have been successively used in
Solvation of Drugs: DESs could readily solvate organic macromole- chemoselectively reduce epoxides, aldehydes, and ketones (except Aryl
cules, which are otherwise only sparingly soluble in water, and thus open ketones and aryl imines) using reducing agents like NaBH4 and AlH3.
possible avenues for oral drug delivery in pharmacological applications. These reductions take very long time, and have low reactivity with
A study carried out by Morrison and team showed improved solubility of various carbonyl compounds in the absence of DESs as solvents, on top of
some sparingly water-soluble drugs, viz. danazol, itraconazole, griseo- that, these also employ highly flammable and toxic organic solvents such
fulvin, benzoic acid in DESs of ChCl-urea and ChCl-malonic acid in as, methanol and 2-propanol. The experimental procedure for the same
presence and absence of water. DESs improved the solubility by was also simplified in the presence of DESs, as the reactants were only
5–22,000 times than that in pure water. The higher oral LD50 values of supposed to mix for a duration so as to obtain the product in fairly good
DESs with rats and mice promoted it as a safer solvent to dissolve drugs yields. Using DESs as a substitute solvent has an advantage to the reac-
[62]. Studies have also shown that biomolecules could form stable sec- tion, that the scientists were also able to reduce a diverse variety of
ondary structures in DESs, which could be reversibly denatured [63]. carbonyl compounds, viz. saturated, unsaturated, hetero aryl, and aro-
DESs could be explored for plethora of life sciences applications [33]. matic aldehyde and ketones as in Scheme 2. Ortho-substituents did not
Organic Synthesis: Solvent choice is important in the area of the hinder the reduction either. DESs also facilitated the reduction of epox-
catalysis or organic synthesis. Identify the better solvents is important ides in a rather mild and Lewis acid-base free environment. Yield as high
because it is not only permitting the superior connection in between the as 95% was obtained in relatively less time, and a variety of commercially
catalysts as well as reactants but additionally the strategies of disposal, available epoxides have been reduced [67].
reusing as well as the techniques of stir up is also determined. Use of DESs On reacting dione and the amine in equal mole at 80
C for 2 h in
in the place of organic solvents, have facilitated the reducibility of the ChCl/urea for 2 h optimum yield is obtained as in Scheme 3. The pyrrole
cost of a process, as well as its ecological footprint. Moreover, as the formed in product is simply extracted by dissolving the product into ethyl
components of DESs are aggregated through hydrogen bonds, and as they ethanoate or diethyl ether. Because DESs is not soluble in ethyl ethanoate
are fairly polar [64] - they can dissolve a variety of compounds, and or diethyl ether and it can be recovered by evaporating using rotavap.
unusual combination of compounds. Thus, DESs have a very firm stance Recovered DESs can be used up to four times with no alteration in its
in their usage in organic synthesis as in Fig. 9 [65]. yield [68].
DESs based on urea, carbohydrates, inorganic salts have been re- Same reaction is carried out in ChCl/glycerol keeping all the condi-
ported as a novel solvent, catalyst and reactant for Biginelli reaction (to tion same (temperature, time and concentration) Scheme 4 and it is
synthesize dihydropyrimidone (DHPM) derivatives, which are important observed that reaction proceed less effectively as compared to Scheme 3
structure in natural products and are important pharmacophore) and and yield is only 67% but when reaction time is increased for 12 h 90%
proved to eliminate harsh conditions, toxic organic solvents, Lewis and yield is observed [68]. This change is observed due to weak hydrogen
Bronsted acids which are involved in the reaction as in Scheme 1. This bond activation by glycerol as compared to that of urea. From these we
novel modification gave excellent yields at ambient temperature and less can say that DESs can play a role of catalyst in organic synthesis.
time. Apart from the excellent yields obtained, DESs also eliminated Pharmaceuticals, dye intermediates, Agro-chemicals, fine chemicals,
other tedious workups and DHPMs were isolated with high purity [66]. Petro-chemicals, and catalysts for polymerization employ a wide variety
The reductive cleavage of epoxides and reduction of carbonyl of amines and their derivatives. These also have very profound biological

Fig. 9. Applications of DESs in organic synthesis.

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M.B. Singh Mr et al. Journal of the Indian Chemical Society 98 (2021) 100210

Scheme 1. Biginelli reaction between 4-nitrobenzaldehyde and ethyl acetoacetate in different melts to yield DHPM.

Scheme 2. Reduction of carbonyl compounds in DESs (reline).

Scheme 3. Paal-Knorr synthesis.

Scheme 4. Paal Knorr synthesis using CC/G (DESs).

activities and are used as antihistamine, antihypertensive, anti- inherently difficult to produce selectively in organic solvents as even in
inflammatory drugs. THe DES (ChCl: urea in 1:2 M ratio) has been low concentration of alkylating agents, poly alkylated products are pro-
found to selectively produce mono N-alkylated amine, which is duced. While, in the same study, enzyme lipase was employed for the

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M.B. Singh Mr et al. Journal of the Indian Chemical Society 98 (2021) 100210

same purpose, and it is far better than the DES's yield. compounds which are like NADES are stimulate the cryoprotective
Research in medicinal field is always to develop and create new ways agents which help to stop the ice formation in cells, chaperonins; is a
for the delivery of medications; are lifesavings and can treat the target small molecule to assist refolding of proteins.
areas effectively, and for the delivery of drugs, therefore, the promising BIOMASS PROCESSING: Biomass is the process in which utilization
characteristics of DESs have create curiosity to them like as potential of resources from living resources has been investigated or explored,
vehicles. For the advancement in the research field of medicine, the use because the waste of plants is cheap, extensively abundant and renew-
of DESs for the delivery of drug create many options for better pharma- able. With the help of process of fermentation polysaccharides, cellulose
ceuticals is huge fascinate potential. Primarily, notices efforts, a large and also hemicelluloses has been utilized from this waste for the gener-
number of varieties of organic compounds, which have an ability to be ation of biomass, renewable energy as well as biochemicals. Kim et al.
used for the formation of deep eutectic liquids and suggested that deep [72] studied that the DESs are capable of being recovered as well as
eutectic solvents can be handed as solubilization vehicles of drug, for reusable in processing of biomass is shows importance and he observed
example, numerous medicine; (lidocaine/prilocaine) – these are very the recuperation of DESs, which can be used in the functioning of
transient, acceptability, stabilize mild skin and skin redness is the adverse switchgrass. After the several cycles of forced separation method of ul-
effect of it which occur to it. A great work of how medicine and liquids trafiltration, almost 95% of DESs was recovered.
which are deep eutectic could be associated wisely. BIOCATALYSIS: Formation of C-C bond, epoxidations and Trans-
The added advantage with the DES over lipase was that, it was easy to esterifications, these are the reactions which are facilitated by similar
prepare (mixing choline chloride in urea in 1:2 M ratio and heating at microbes or enzymes as catalysts in biocatalysis process. Biocatalysis can
74
C till a clear solution was obtained, and no further purification was also be defined as a branch of organic chemistry. The study of natural
required), easy to handle, and more recyclable than the enzyme with framework is included by it where this take place, also attempt to develop
little reduction of yield as compared to lipase, after several cycles novel reactions that could be facilitate by biocatalysis. This is the process
(Fig. 10) [69]. carried out in aqueous solution and there should be high priority in the
Lu et al. [70] explains about the increased solubility of some com- careful selection of both enzymes and solvent. For the process of bio-
pounds in DESs which are ibuprofen, aspirin, naproxen, and also about catalysis or to indicate the appreciable potential to facilitate up to date
acetaminophen. Few drugs face a problem in the stability in aqueous pathway of biocatalytic, DESs gives numerous key characteristics. DESs
solution because of their low molecular weight. Lu et al. also tested the shows many properties for the facilitation of new pathways in bio-
solubility of organic compounds in DES to confirm that eutectic mixture catalysis. The main quality as liquid with capability to support a huge
helps in solubility or not. And after this, the result shows that the sol- variation of enzymes, substrates and further bioactive solutes, to
ubulity of organic compounds increases in DESs. assemble them as potential contender. Due to the attentive selection of
DESs have modified the frontal polymerization (FP) by reducing the components, DESs behave as “potential media which is non-conven-
energy requirement for the process and quenching the propagation of the tional”. DESs could be served as substrate as well as reaction medium
polymerization, which is otherwise uncontrollable in organic solvents facilitating reaction which cannot be done in the completely aqueous
and ILs. Choline chloride based DESs of acrylic acid and methacrylic acid medium.
were employed for the same and the observations of the FP revealed that POWER SYSTEM TECHNOLOGIES: In smart phones, laptops and
these DESs controlled the front temperature (which otherwise leads to computers, there is considerable requirement for techniques and mate-
burnout of initiator and monomer boiling), and moreover, these partic- rials to upgrade the technologies of energy conversion or storage due to
ular DESs also served as reactant for acrylic polymerizations. Polymer the rechargeable batteries’ ubiquity, involving safety, protection and
conversion was improved up to 75% in ChCl: acrylic acid DES and 85% in functionality. Numerous failures of batteries have been resulted due to
ChCl: methacrylic acid DES [71]. the current electrolytes which are used in batteries of lithium-ion (LIBs),
Microheterogeneity in Novel Deep Eutectic Solvents: In the pro- and there is the probability of a substitute that is flame-resistant which
cess of extraction, the presence of hydrophobic DESs and also applied has not compromise in different areas is attractive [33]. For LIBs, DESs
strongly in this process lead to the studies of micro-heterogeneity in are being examined as electrolytes which are potential, Because of
DESs. With the help of Li þ ClO-4 along with propionamide as well as excessive conductivity, compress flammability, and broad range of liquid
acetamide molecular active simulation found heterogeneity which DESs are contemplate as potential electrolytes for batteries of lithium-ion
nanoscale endemic. And on glycerol arrangement with choline chloride, (LIBs). Favorable features and high stability of electrochemicals for LIBs
the difference in groups of non-polar and polar was accomplished. has been achieved during the testing on various DESs. Storage technique
Associated molecular dynamic and IR work also shows the evidence of has main advantage and it has expandable storage option of energy as
MH in DESs. well as very demanding; the efficiency of energy depends upon the
SYNTHESIS OF NANOMATERIALS: From the numerous studies, it quantity of catholyte and anolyte that can be placed in the tank, and this
has been observed that DESs can applied successfully in nanotechnol- is made for an appropriate long-term solution of energy storage or con-
ogies and related field . Micro-heterogeneity in DESs has been the field of servation whose time is short. However, this technique has a major hitch,
desirous interest. Some of the structures like glyceline, reline as well as have difficulty in detecting competent electrolyte candidates which are
ethaline have been investigated and these structures shows the electric cheap, safe to the environment and also abundant. In few areas of gen-
potential functions when come in contact with electrodes of graphite. At eration of power DESs act as a promising solvent.
negative as well as positive potentials of the stern layer, the cation TOXICITY OF DESs: Javier et al. [73] reported that the toxicity and
(choline) and the anion (chloride) get attracted. biodegradability of DESs were determined by the types and structure of
NUCLEIC ACID GENOMICS: In the area of genomics, DESs have been their constituent. Some of the investigated DESs had antifungal action
used for the advancement of this field, and genomics is basically the and acute toxicity against fish. In comparison, ChCl based DESs were
study or research of nucleic acid (DNA/RNA) as well as genome of or- more harmful than that N,N-diethyl ethanol ammonium chloride (EAC)
ganisms, and also technologies which is related to it. Because of the DESs. Type III DESs (organic salt and HBD) were observed to be less toxic.
liquid conditions offered by DESs, DNA novel nature has been remarked. Moreover, the toxicity of the DESs and their constituent differed
DESs having a mixture of 1:1 M ratio of acetic acid and choline chloride depending on the organism examined. Even after dissolution in aqueous
work like a catalyst of speedy fibrillation of lysozyme. Most of the DESs solution, the hydrogen bonding occur in DES has shown their impact of
accommodate natural chief metabolites comprises organic acids, sugar toxicity towards organisms.
alcohols, amines as well as amino acids (supposed to survive at lowest or Ibrahim et al. [74] reported that doses between 0 and 300 mM, the
negative temperature) due to these metabolites. Researchers showed DESs are not harmful to E. coli and perhaps to other related species. DESs
interest in it for the exploration of DESs, for instance in plants, used in this concentration range may be considered as “environmentally

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M.B. Singh Mr et al. Journal of the Indian Chemical Society 98 (2021) 100210

Fig. 10. Variation of recycled yield of catalysts.

benign”. Cells may resist DESs concentration between 300 mM and macromolecules such as DNA, RNA and enzymes. DESs are very viscous
450 mM even though, it has a little impact on the cellular and metabolic liquids, may be one major drawback of DESs. Efforts are being put to
activates (typically microbial growth curve shifted to diauxic-diphasic or derive relatively less viscous DESs for practical usage. Viscosity of DESs is
triauxic -triphasic- curve and lag time are also longer than at lower DESs temperature dependent and has been explained on the basis of Hole
concentration). When the concentration of DESs is above 600 mM it more theory. Consequently, the ionic conductivity is also feeble, and varied in
toxic resulting the inhibition of total growth. The toxicity is related to the compliance to Arrhenius-like theory. DESs are also denser than water and
significant acidity of the of the medium generated by DESs hydrolysis as fairly polar-thus can be utilized as non-aqueous substitute to water in
well as the chemical composition of the DESs. Therefore, doses greater many separation processes. Deep eutectic mixture is distinct from normal
than 600 mM might be used as bactericide or even to investigate its eutectic mixture due to abnormally low melting point of the eutectic
possibility in inhibitory impact on tumoral cells. mixture, thus, the term “Deep” is prefixed to mark this distinction. The
properties of DESs have been successfully utilized in many processes, and
Conclusion many more applications are further hypothesized. The high polarity of
DESs have been utilized in purification of bio-diesel, they can removed
Ionic liquids (ILs) and deep eutectic solvents (DESs) are better sub- up to 99% of glycerol generally found as an impurity in bio-diesels. DESs
stitutes to organic solvents in synthesis, extraction and separation pro- have very high distribution coefficient of solutes, and even dissolves
cesses, as they are practically non-volatile, broad liquidous range, gases and metal oxides selectively. Moreover, they also readily dissolve
thermally stable, non-flammable and their properties could be tuned as organic macromolecules, thereby becoming useful in pharmacological
per the requirements of the process. However, the green affiliation of ILs applications. A number of organic synthesis have been carried out using
have been contradicted and their toxicity profile is of a great concern. DESs as a solvent or catalytic medium, and they were recovered almost
DESs have been proven to have relatively less toxicity and cytotoxicity entirely after the process. DESs are thus very viable replacement of ILs
than ILs. DESs and ILs have many common physicochemical properties and harmful organic solvents, and have been so far proved to be useful in
and thus DESs could be invariably used in place of ILs for various pro- many applications. Moreover, their physicochemical properties project
cesses. Moreover, their synthesis is very simple: their components are innumerous applications which are yet to be explored.
required to be mixed in a characteristic molar ratio. This process is 100%
atom economic and thus no waste is formed, and many work-up pro-
cesses are eliminated. Thus, DESs stand out a greener and cheaper Declaration of competing interest
neoteric solvent. natural deep eutectic solvents (NADESs), are a sub-class
of DESs, and are derived from primary plant metabolites. These emerge “I, Prashant Singh (the Corresponding Author), declare that this
as a very environment friendly solvent and are also expected to be manuscript is original, has not been published before and is not currently
forming an alternate media to water and lipids to carry out important being considered for publication elsewhere. I further confirm that the
processes in plants under drastic conditions, such as drought and cold. order of authors listed in the manuscript has been approved by all of us.
These were also found to dissolve water-insoluble metabolites and There is also no conflict of interest in any way.

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M.B. Singh Mr et al. Journal of the Indian Chemical Society 98 (2021) 100210

Appendix A. Supplementary data [27] Flieger J, Flieger M. Ionic liquids toxicity-benefits and threats. Int. J. Mol. Sci. 2020;
21:6267. https://doi.org/10.3390/ijms21176267.
[28] Cho C-W, Pham TPT, Zhao Y, Stolte S, Yun Y-S. Review of the toxic effects of ionic
Supplementary data to this article can be found online at https://do liquids. Sci. Total Environ. 2021;786:147309. https://doi.org/10.1016/
i.org/10.1016/j.jics.2021.100210. j.scitotenv.2021.147309.
[29] Gonçalves ARP, Paredes X, Cristino AF, V Santos FJ, Queir os CSGP. Ionic liquids—a
review of their toxicity to living organisms. Int. J. Mol. Sci. 2021;22. https://
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